EURETINA Lecture focuses on gene therapy for retinal diseases

Retinal gene therapy will become a huge component of medical retina treatments within the current generation, according to Prof 

Robert MacLaren FRCOphth, FRCS, who delivered this year’s EURETINA Lecture 2014 as part of the Opening Ceremony at the 

14th EURETINA Congress. 

In a broad overview of the current state of play in gene therapy research for retinal diseases, Prof MacLaren, professor of 

ophthalmology at the University of Oxford and consultant ophthalmologist at the Oxford Eye Hospital, told delegates that significant 

progress has been made in recent years in developing safe and effective gene therapies for incurable retinal diseases such as 

choroideremia.

The first results of the gene therapy clinical trial for choroideremia which were published early in 2014 showed very promising 

initial results, and surpassed the expectations of the researchers involved, said Prof MacLaren.

The main aim of that study was to deliver gene therapy into the cells in the retina of the eye of the six enrolled patients without 

causing damage. 

The gene therapy approach developed by Prof MacLaren’s team used a small, safe adeno-associated viral (AAV2) vector to 

carry the missing choroideremia gene into the light-sensing cells in the retina. To inject the virus, the patient’s retina was first 

detached and then the virus was injected directly into the subretinal space.

After six months, the patients showed significant improvements in vision in dim light and two of the six were able to read more 

lines on the eye chart.

Prof MacLaren said that the choroideremia study is in many respects the ideal model for gene therapy in other incurable retinal 

diseases. 

“The results show the potential for gene therapy, not just in the treatment of choroideremia, but also for other chronic retinal 

degenerations that require early intervention before the onset of visual loss,” he said.

Encouragingly, the therapeutic benefit in the study was confirmed by initial microperimetry tests and OCT and fundus 

autofluorescence scans which compared the treated and control eye in each patient, said Prof MacLaren.

“Preoperatively we saw in one patient that the microperimetry fixation was quite variable in the region where the fovea existed 

before atrophy. Six months after treatment, the microperimetry shifted its fixation from the previous foveal zone to the treated region 

where the patient had increased sensitivity and this was consistent with the improvement in visual acuity,” he said.

The importance of obtaining objective, measurable data to show a real clinical benefit from treatment cannot be overstated, said 

Prof MacLaren. 

“With these preliminary studies the patients are very desperate to have something which works and it is very important as 

clinicians that we look for clues that the result is a real one and not a placebo effect. The functional and anatomical data we have 

examined so far indicate that this is indeed the case in these choroideremia patients,” he said.

Although this initial trial has helped to answer some of the key questions relating to the safety of gene therapy, many more 

questions concerning the benefits of early intervention, optimal dosing and surgical technique remain to be elucidated in the future, 

said Prof MacLaren.

Prof MacLaren said that the current research is focusing on optimising the AAV delivery vector to enhance gene expression and 

thereby increase the chances of the treatment successfully targeting both the RPE and the photoreceptor cells. 

A full report of Prof MacLaren’s lecture will appear in a future edition of EuroTimes.